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Abstract Title:

Radiosensitizing Effect of Celastrol by Inhibiting G2/M Phase Arrest Induced by the c-myc Gene of Human SW1353 Chondrosarcoma Cells: Network and Experimental Analyses.

Abstract Source:

Biomed Res Int. 2022 ;2022:1948657. Epub 2022 Jan 31. PMID: 35141331

Abstract Author(s):

Jin Qian, Zhen Zhang, Xiao Han, Liulong Zhu, Zhenyu Bian, Tao Xie

Article Affiliation:

Jin Qian

Abstract:

Objective: Studies have unveiled that the components ofHook F (TWHF) such as celastrol could attenuate apoptosis and proliferation of various tumor cells. This study is focused on the radiosensitization effect and apoptotic pathways of celastrol via the inhibition of thegene and the influence of which combined with radiotherapy on the proliferation, apoptosis, invasion, and metastasis of chondrosarcoma cells.

Methods: A variety of bioinformatic tools were applied to explore the expression level and prognosis of thegene in different tumor cells and chondrosarcoma cells. We used pharmacology network to analyze the components, pathways, targets, molecular functions of TWHF and explore the relevant effective components over the MYC gene. Clone formation assay, CCK-8 assay, flow cytometry, and transwell migration assay were applied to detect the effects of celastrol on the expression ofgene, cell apoptosis, and cell cycle. Radiation therapy was used to observe the radiosensitization effect of celastrol on chondrosarcoma.

Results: This study shows that the c-myc gene is overexpressed in various tumor cells and bone tumor cells to varying degrees. Celastrol can significantly inhibit the expression of thegene, induce G2/M phase arrest through regulation of G2/M phase-related proteins, and promote SW1353 cell apoptosis through the mitochondrial signaling pathway. In addition, we also found that the use of triptorubin to inhibitgene expression in combination with radiotherapy can increase the osteosarcoma cells' apoptosis rate through the mitochondrial signaling pathway significantly.

Conclusions: Our study validated the radiosensitization effect of celastrol through knocking down the expression of the c-myc gene to induce G2/M phase arrest and provides a new idea for the treatment of refractory or recurrent chondrosarcoma that is not sensitive to radiotherapy.

Study Type : In Vitro Study

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